This 2021 review summarized three dietary supplements’ effects on psychiatric symptoms:
“Upregulation of Nrf2 has been suggested as a common therapeutic target for major neuropsychiatric disorders. In this paper, evidence is presented showing how NAC [N-acetyl-cysteine], coenzyme Q10 (CoQ), and melatonin can ameliorate many important effects of oxidative stress by upregulating Nrf2.
Given its key role in governing cellular antioxidant response, upregulation of Nrf2 has been suggested as a common therapeutic target in neuropsychiatric illnesses such as major depressive disorder, bipolar disorder, and schizophrenia. These are associated with chronic oxidative and nitrosative stress, characterised by elevated levels of reactive oxygen species, nitric oxide, and peroxynitrite.
- Acts as a superoxide scavenger in neuroglial mitochondria;
- Instigates mitohormesis;
- Ameliorates lipid peroxidation in the inner mitochondrial membrane;
- Activates uncoupling proteins;
- Promotes mitochondrial biogenesis; and
- Has positive effects on the plasma membrane redox system.
- Scavenges mitochondrial free radicals;
- Inhibits mitochondrial nitric oxidesynthase;
- Restores mitochondrial calcium homeostasis;
- Deacetylates and activates mitochondrial SIRT3;
- Ameliorates increased permeability of the blood-brain barrier and intestine; and
- Counters neuroinflammation and glutamate excitotoxicity.”
https://www.researchgate.net/publication/348309816_Increasing_Nrf2_Activity_as_a_Treatment_Approach_in_Neuropsychiatry “Increasing Nrf2 Activity as a Treatment Approach in Neuropsychiatry” (registration required)
These reviewers explored three selected supplements, citing 380 references. They overlooked something, though. There was only one mention of sulforaphane in their paper, yet four references’ titles included sulforaphane?
I take two of the three exogenous supplements discussed. The one I stopped taking over a year ago – NAC – was thoroughly discussed, but not in contexts directly related to the Nrf2 transcription factor. Why?
Switch on your Nrf2 signaling pathway pointed out:
“We use NAC in the lab all the time because it stops an Nrf2 activation. So that weak pro-oxidant signal that activates Nrf2, you switch it off by giving a dose of NAC. It’s a potent antioxidant in that right, but it’s blocking signalling. And that’s what I don’t like about its broad use.”
The current review noted that Nrf2 is activated by oxidative stress. NAC is a precursor to glutathione – our main endogenous antioxidant – and neither one activates Nrf2 pathways.
What does? Sulforaphane.